Myocardial ischaemia reperfusion injury (MIRI) is considered the primary cause of death in patients with cardiovascular diseases. Recently, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been found to be involved in the pathogenesis of MIRI. However, whether lncRNA ROR and miR-124-3p play roles in MIRI and the underlying mechanism remain undetermined. HCMs were exposed to hypoxic conditions for 2 h followed by re-oxygenation (H/R) treatment. Expression of miR-124-3p and lncRNA ROR in HCMs was measured by qRT-PCR. TRAF6 expression was evaluated by qRT-PCR and western blotting. ELISA and qRT-PCR were conducted to assess the production of TNF-α, IL-6, and IL-1β. The interaction between miR-124-3p and TRAF6, as well as between miR-124-3p and lncRNA ROR, was verified by dual-luciferase reporter assay. Cell apoptosis was detected by flow cytometry analysis. Our data revealed that miR-124-3p was significantly downregulated, while TRAF6 and lncRNA ROR were upregulated in both MIRI rat model and H/R treated HCMs. Overexpression of miR-124-3p reversed the H/R-induced cell apoptosis and upregulation of TNF-α, IL-6, and IL-1β. Mechanistically, miR-124-3p bound and negatively regulated TRAF6 expression in HCMs. Moreover, TRAF6 overexpression significantly blocked the effects of miR-124-3p mimics on cell apoptosis and inflammatory response of HCMs, which involved the NF-κB pathway. Further analysis showed that lncRNA ROR sponged and negatively regulated miR-124-3p in HCMs. Overexpression of IL-1β was demonstrated to promote H/R induced cell apoptosis in HCMs. In addition, overexpression of ROR further enhanced the H/R-induced inflammation and cell apoptosis through its action on miR-124-3p. The lncRNA ROR/miR-124-3p/TRAF6 axis regulated the H/R-induced cell apoptosis and inflammatory response of HCMs.

中文翻译：

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lncRNA ROR / miR-124-3p / TRAF6轴调节了人心肌细胞中缺血再灌注损伤诱导的炎症反应。

心肌缺血再灌注损伤（MIRI）被认为是心血管疾病患者的主要死亡原因。最近，已发现长的非编码RNA（lncRNA）和微小RNA（miRNA）参与了MIRI的发病机理。但是，lncRNA ROR和miR-124-3p是否在MIRI中发挥作用，其潜在机制仍不确定。将HCM暴露于低氧条件下2小时，然后进行再充氧（H / R）处理。通过qRT-PCR测量miR-124-3p和lncRNA ROR在HCM中的表达。通过qRT-PCR和蛋白质印迹评估TRAF6表达。进行ELISA和qRT-PCR评估TNF-α，IL-6和IL-1β的产生。通过双荧光素酶报告基因分析验证了miR-124-3p与TRAF6之间以及miR-124-3p与lncRNA ROR之间的相互作用。通过流式细胞术分析检测细胞凋亡。我们的数据显示，在MIRI大鼠模型和H / R治疗的HCM中，miR-124-3p显着下调，而TRAF6和lncRNA ROR上调。miR-124-3p的过表达逆转了H / R诱导的细胞凋亡以及TNF-α，IL-6和IL-1β的上调。从机制上讲，miR-124-3p结合并负调控HCM中的TRAF6表达。此外，TRAF6的过表达显着阻断了miR-124-3p模拟物对涉及NF-κB通路的HCM细胞凋亡和炎症反应的影响。进一步的分析表明，lncRNA ROR使HCM中的miR-124-3p失控。IL-1β的过表达可促进H / R诱导的HCM细胞凋亡。此外，ROR的过表达通过其对miR-124-3p的作用进一步增强了H / R诱导的炎症和细胞凋亡。lncRNA ROR / miR-124-3p / TRAF6轴调节H / R诱导的细胞凋亡和HCM的炎症反应。